Fusion-proteins as biopharmaceuticals--applications and challenges.

As the genetic combination of originally separate proteins, fusion proteins are successful biopharmaceuticals. This review summarizes the fusion proteins that are approved for use in the clinic and those that are currently in clinical trials. Fusion proteins can be categorized into several groups according to their features. In the first group, effector molecules are fused to Fc domains, albumin or transferrin to extend the plasma half-life of the fusion product. In the second group, toxicity is conveyed by fusion proteins to toxins, enzymes or cytokines. The third application, which is not yet in clinical trials, utilizes fusion partners to enable novel delivery and targeting routes. Besides some specific disadvantages, many examples of fusion proteins suffer from the challenge of immunogenicity; however, future applications with novel fusion partners will reach beyond cancer, immunology and inflammation.